Lortenza tablets p/o 100mg/5mg №10×3

Name:
Lortenza tab., coating captivity. vol., 100mg 5mg in a blister. in pack. No. 10×3
Description:
tab., cover. film coated, 5 mg + 50 mg: 28 or 30 pcs. Reg. №: 10483/16 dated 06/06/2016 – Active Tablets, film-coated light brown with an orange tint, oval, slightly biconvex. 1 tab. amlodipine besylate 6.94 mg, which corresponds to the content of amlodipine 5 mg losartan A substance-granules 163.55 mg, which corresponds to the content of losartan potassium 50 mg Excipients: cellactose 80 (alpha-lactose monohydrate, cellulose powder), microcrystalline cellulose, pregelatinized starch, starch corn (maize), sodium starch glycolate, yellow and/or red iron oxides, anhydrous colloidal silicon dioxide, magnesium stearate, white opadry II (partially hydrolyzed polyvinyl alcohol, titanium dioxide, macrogol, talc). 7 pcs. – blisters (4) – packs of cardboard. 10 pieces. – blisters (3) – packs of cardboard. The main active ingredient losartan + amlodipine Release form Tablets 100 mg 5 mg Dosage The drug is taken orally, 1 time / day, regardless of the meal time, with a small amount of water. The recommended dose of Lortenza® is 1 tab./day. The drug Lortenza® at a dose of 5 mg + 50 mg is prescribed to patients who have not achieved adequate blood pressure control when using amlodipine at a dose of 5 mg or losartan at a dose of 50 mg as monotherapy. Lortenza® at a dose of 5 mg + 100 mg is prescribed to patients who have not achieved adequate blood pressure control when using losartan at a dose of 100 mg or Lortenza® at a dose of 5 mg + 50 mg. Lortenza® at a dose of 10 mg + 50 mg is prescribed to patients who have not achieved adequate blood pressure control when using amlodipine at a dose of 10 mg or Lortenza® at a dose of 5 mg + 50 mg. The drug Lortenza® at a dose of 10 mg + 100 mg is prescribed to patients who have not achieved adequate blood pressure control when using the drug Lortenza® at a dose of 5 mg + 100 mg or 10 mg + 50 mg. The dose is selected after the previously performed dose titration of the individual components of the drug. If a change in the dose of one of the active ingredients in the fixed combination product is required (for example, due to a newly diagnosed disease, a change in the patient’s condition or drug interaction), an individual selection of doses of individual components is necessary. The maximum daily dose is 10 mg + 100 mg. Patients taking both losartan and amlodipine can be switched to Lortenza® containing losartan and amlodipine at the same doses. In patients with impaired renal function with CC from 50 to 20 ml / min, dose adjustment is not required. The drug Lortenza® is contraindicated in patients with CC less than 20 ml / min and in patients on hemodialysis. Patients with impaired liver function (less than 9 points on the Child-Pugh scale) in history are recommended to use losartan at lower doses. Due to the lack of a dosage containing 25 mg of losartan in Lortenza®, this dose should be administered in monotherapy with losartan. The use of the drug Lortenza® is possible in patients with impaired liver function (less than 9 points on the Child-Pugh scale), who, according to the decision of the doctor, are recommended to use losartan at a dose of 50 mg. In patients with reduced BCC (for example, due to treatment with high doses of diuretics), the initial dose of losartan should be reduced to 25 mg 1 time / day. Due to the lack of a dosage containing 25 mg of losartan in Lortenza®, this dose should be administered in monotherapy with losartan. Before using the drug Lortenza®, it is necessary to restore the BCC and the sodium content in the blood plasma. In elderly patients, dose adjustment of Lortenza® is not required, but the dose should be increased carefully. The drug Lortenza® should not be prescribed to children and adolescents under the age of 18 years, because. there are no data on the efficacy and safety of use in this group of patients. Patients with reduced BCC In patients with reduced BCC (for example, when taking diuretics in high doses, severe diarrhea, vomiting and other conditions leading to hypovolemia), symptomatic arterial hypotension may develop at the beginning of therapy with Lortenza®. Before using Lortenza®, the BCC deficiency must be eliminated. For patients in whom the daily dose of losartan is 25 mg, the use of Lortenza® is not recommended. Precautions related to amlodipine Due to the long T1 / 2, vasodilation that has developed as a result of taking amlodipine may persist after its withdrawal. Thus, the use of another vasodilator after discontinuation of amlodipine should be carried out with caution, with an individual assessment of the dose, dosing interval and active monitoring of the patient’s condition. During the period of treatment, it is necessary to control body weight and salt intake, an appropriate diet should be prescribed. It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gum hyperplasia). Precautions related to losartan Hyperkalemia (plasma potassium >5.5 mmol/l) was observed in 1.5% of patients taking losartan as monotherapy. None of these cases required discontinuation of the drug. The simultaneous use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride, eplerenone), potassium preparations, potassium-containing salt substitutes, as well as drugs that can lead to an increase in plasma potassium (eg, heparin), with losartan should be justified ( especially in elderly patients with impaired renal function), and the content of potassium in the blood plasma should be regularly monitored. Taking losartan can lead to transient arterial hypotension, accompanied by shock, fainting and shortness of breath. The drug Lortenza® should be used with caution in patients: with reduced BCC; on a salt-restricted diet. Hypersensitivity reactions In patients with a history of angioedema (swelling of the larynx, vocal cords, face, lips, pharynx and / or tongue), it is necessary to control the use of the drug Lortenza®. Aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy As with all drugs that have a vasodilatory effect, angiotensin II receptor antagonists should be used with caution in patients with aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy. Chronic heart failure As with the use of other drugs that have an effect on the RAAS, in patients with CHF and with or without impaired renal function, there is a risk of developing severe arterial hypotension or acute renal dysfunction. Because there is insufficient experience with the use of losartan in patients with CHF and concomitant severe renal impairment, in patients with severe heart failure (NYHA class IV), as well as in patients with heart failure and symptomatic life-threatening arrhythmias, Lortenza should be used with caution in patients of these groups. IHD and cerebrovascular disease As with all vasodilatory drugs, angiotensin II receptor antagonists should be used with caution in patients with coronary artery disease or cerebrovascular disease, since an excessive decrease in blood pressure in this group of patients can lead to the development of myocardial infarction or stroke. Primary hyperaldosteronism in patients with primary hyperaldosteronism, as a rule, there is no positive response to therapy with antihypertensive drugs that act by inhibiting the RAAS, the use of Lortenza® is not recommended in this group of patients. Patients with hepatic insufficiency Data from pharmacokinetic studies indicate that in patients with cirrhosis of the liver, there is a significant increase in the concentration of losartan in plasma. The use of the drug Lortenza® is not recommended in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale), as well as in patients with hepatic insufficiency (less than 9 points on the Child-Pugh scale), who are recommended to reduce the dose of losartan to 25 mg / day. day Patients with renal insufficiency Due to inhibition of the RAAS in some predisposed patients treated with losartan, changes in renal function that are reversible upon discontinuation of the drug were observed. In patients whose renal function may depend on the activity of the RAAS (for example, with CHF III-IV FC according to the NYHA classification), the use of ACE inhibitors was accompanied by oliguria and / or increasing azotemia and, rarely, acute renal failure and / or death. A similar picture was observed with the use of losartan in these patients. In clinical studies, the use of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis resulted in an increase in the concentration of creatinine and residual urea nitrogen in the blood plasma. A similar effect was observed when taking losartan in this group of patients, it was reversible when the drug was discontinued. Lortenza® should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney. Excipients Lortenza® contains lactose, so the drug should not be used in the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome. Influence on the ability to drive vehicles and control mechanisms Care should be taken when driving vehicles and working with other technical devices that require increased concentration of attention and speed of psychomotor reactions, given the possibility of dizziness, headache, drowsiness, fatigue or nausea, especially at the beginning of treatment . Pharmacodynamics Lortenza is a combination of two active ingredients with complementary antihypertensive effects: amlodipine (BCC) and losartan (angiotensin II receptor antagonist – ARA II). The active components of the drug have a different mechanism of antihypertensive action: amlodipine causes vasodilation, reducing peripheral vascular resistance, losartan affects the RAAS (inhibits the effects of angiotensin II), which leads to a more pronounced decrease in blood pressure compared to that during monotherapy with each drug. Amlodipine A derivative of dihydropyridine that blocks calcium channels and reduces the transmembrane current of calcium ions into cardiomyocytes and vascular smooth muscle cells. The antihypertensive effect of amlodipine is associated with a direct relaxing effect on the smooth muscles of arterial vessels. In preclinical studies, amlodipine had a more pronounced effect on vascular smooth muscle cells compared to cardiomyocytes. Amlodipine does not adversely affect either AV conduction or myocardial contractility. Reduces vascular resistance of the kidneys and increases renal blood flow. Studies of amlodipine in patients with CHF II-IV functional class according to the NYHA classification (classification of the New York Heart Association) showed that amlodipine does not adversely affect exercise tolerance, ejection fraction, or plasma lipid and glucose concentrations. After a single oral dose of amlodipine, the effect begins after 2-4 hours and lasts for 24 hours. The maximum antihypertensive effect is achieved no earlier than 4 weeks after the start of therapy. Amlodipine reduces blood pressure in patients in the supine and sitting position, as well as during exercise. Due to the gradual development of the pharmacodynamic effect, amlodipine does not cause a sharp decrease in blood pressure or reflex tachycardia. Amlodipine reduces the severity of left ventricular hypertrophy. Hemodynamic effects remain unchanged with long-term use of amlodipine. Losartan Synthetic ARA II (type AT1) for oral administration. Angiotensin II is a powerful vasoconstrictor, the main active hormone of the RAAS, and an important determining pathophysiological link in the development of arterial hypertension (AH). Angiotensin II binds to AT1 receptors found in many tissues (vascular smooth muscle, adrenals, kidneys, and heart) and performs important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of vascular smooth muscle cells. Losartan selectively blocks AT1 receptors. Losartan and its pharmacologically active carboxylated metabolite (E-3174), both in vitro and in vivo conditions, block all physiological effects of angiotensin II, regardless of the source or route of its synthesis. Losartan does not have agonist properties and does not block receptors for other hormones or ion channels involved in the regulation of cardiovascular activity. Losartan does not inhibit ACE, which destroys bradykinin. Accordingly, it does not cause an increase in the frequency of undesirable effects mediated by bradykinin. Suppression of the regulation of renin secretion under the action of angiotensin II by the mechanism of negative feedback in the treatment of losartan causes an increase in plasma renin activity (ARP) in the blood, which leads to an increase in the concentration of angiotensin II in the blood plasma. However, the antihypertensive effect and a decrease in the concentration of aldosterone in the blood plasma persist, indicating an effective blockade of AT1 receptors. After discontinuation of losartan, the blood ARP and the concentration of angiotensin II in the blood plasma decrease within 3 days to the initial values. Pharmacokinetics Amlodipine Absorption. When taken orally in therapeutic doses, amlodipine is well absorbed. Cmax in plasma is reached after 6-12 hours. Absolute bioavailability ranges from 64 to 80%. Eating does not affect the absorption of amlodipine. Distribution. Vd is about 21 l/kg. Css in blood plasma is achieved 7-8 days after the start of the drug. Plasma protein binding – 98%. Metabolism. Amlodipine undergoes slow but active hepatic metabolism with no significant first pass effect. Metabolites do not have significant pharmacological activity. Withdrawal. The final T1 / 2 from blood plasma is 30-40 hours. Plasma clearance is 7 ml / min / kg. Approximately 60% of metabolites and 10% of unchanged amlodipine are excreted by the kidneys, 20-25% – through the intestines. Pharmacokinetics of special groups of patients Patients with impaired liver function. Experience with the use of amlodipine in patients with hepatic impairment is limited. In patients with impaired liver function, T1 / 2 lengthening is noted. Losartan Absorption. After oral administration, losartan is well absorbed. The systemic oral bioavailability of losartan is approximately 33%. Cmax of losartan and its active metabolite in blood plasma are reached after 1 and 3-4 hours, respectively. Distribution. Losartan and its active metabolite are 99% bound to plasma proteins (mainly albumin). Vd losartan is 34 liters. Metabolism. Losartan is metabolized during the primary passage through the liver with the formation of an active carboxylated metabolite (E-3174) and other inactive metabolites. Approximately 14% of an intravenous or oral dose of losartan is converted to its active metabolite. Following oral or intravenous administration of carbon-labeled potassium losartan (14C losartan), most of the radiolabel in the bloodstream was consistent with losartan and its active metabolite. The minimum level of biotransformation of losartan into its active metabolite was observed in approximately 1% of patients participating in clinical studies. Withdrawal. The plasma clearance of losartan and its active metabolite is 600 and 50 ml/min, respectively. The renal clearance of losartan and its active metabolite is 74 and 26 ml/min, respectively. When losartan is taken orally, about 4% of the dose is excreted by the kidneys unchanged and 6% of the dose is excreted by the kidneys as an active metabolite. The pharmacokinetics of losartan and its active metabolite are linear when taken orally at doses up to 200 mg. When administered orally, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final half-life of about 2 and 6-9 hours, respectively. At a dose of 100 mg taken once a day, neither losartan nor its active metabolite accumulate in plasma. Losartan and its metabolites are excreted by the kidneys and through the intestines with bile. When administered orally and intravenously with 14C losartan in humans, about 35 and 43% of the radioactivity of losartan and its active metabolite, respectively, was excreted by the kidneys, 58 and 50%, respectively, through the intestines. Pharmacokinetics of special groups of patients Elderly patients. Plasma concentrations of losartan and its active metabolite in elderly patients with hypertension do not differ significantly from those in young patients with hypertension. Floor. Plasma concentrations of losartan in women with hypertension were 2 times higher than those in men with hypertension. The concentrations of the active metabolite in men and women did not differ. Patients with impaired liver function. In patients with mild and moderate alcoholic cirrhosis of the liver, when losartan was taken orally, the plasma concentrations of losartan and its active metabolite increased by 5 and 1.7 times, respectively, compared with those in young healthy male volunteers. Patients with impaired renal function. The concentration of losartan in plasma does not change in patients with Cl creatinine more than 10 ml / min. The AUC of losartan in patients on hemodialysis was approximately 2-fold higher than the AUC of losartan in patients with normal renal function. Plasma concentrations of the active metabolite did not change in patients with impaired renal function or in patients on hemodialysis. Losartan and its active metabolite are not excreted by hemodialysis. Indications for use Arterial hypertension (patients who are indicated for combination therapy with amlodipine and losartan). Dosage and administration Inside, 1 time / day, regardless of the time of admission, write with a small amount of water. The recommended dose of Lortenza is 1 tab./day. The drug Lortenza at a dose of 5 mg + 100 mg is prescribed to patients who have not achieved adequate blood pressure control when using losartan at a dose of 100 mg or Lortenza at a dose of 5 mg + 50 mg. Use during pregnancy and lactation Pregnancy The use of the drug Lortenza during pregnancy is contraindicated, if pregnancy occurs, you should immediately stop taking the drug. Drugs that act on the RAAS can cause damage and death of the fetus and newborn when used in pregnant women. Isolated cases of the use of ACE inhibitors during pregnancy are described. The use in the II and III trimesters of pregnancy of drugs that directly affect the RAAS is associated with such fetal damage and complications in newborns as arterial hypotension, neonatal hypoplasia of the skull bones, anuria, reversible and irreversible renal failure. There have also been cases of oligohydramnios, presumably developed as a result of reduced kidney function in the fetus. In these cases, oligohydramnios was associated with limb contractures, craniofacial deformities, and fetal lung hypoplasia. In addition, there have been cases of preterm birth, intrauterine growth retardation and patent ductus arteriosus, but no association with the use of angiotensin II receptor antagonists in these cases was found. The listed side effects, apparently, are not a consequence of the use of angiotensin II receptor antagonists in the first trimester of pregnancy. Pregnant women who took angiotensin II receptor antagonists in the first trimester of pregnancy should be informed about the consequences of taking this group of drugs in the second and third trimesters of pregnancy. Depending on the gestational age, a stress test, a non-stress test, or a fetal biophysical profile can be used to assess the functional state of the fetus. Patients and physicians should be aware that oligohydramnios develops when there is irreversible damage to the fetus. Newborns whose mothers took angiotensin II receptor antagonists during pregnancy should be under medical supervision, given the risk of arterial hypotension, oliguria and hyperkalemia. With the development of oliguria, first of all, correction of blood pressure and renal perfusion is necessary. Exchange transfusion or hemodialysis is necessary to correct arterial hypotension and / or to replace kidney function. Amlodipine The safety of amlodipine during pregnancy has not been established. In animal studies, signs of reproductive toxicity have been observed with high doses of amlodipine. The use of amlodipine during pregnancy is possible in the absence of safe antihypertensive alternative therapy, and if the potential benefit to the mother outweighs the possible risk to the fetus. Losartan The use of drugs that act on the RAAS in the II and III trimesters of pregnancy can cause serious damage or even death of the fetus, therefore, when planning pregnancy or when it occurs, you should stop taking losartan and, if necessary, transfer the patient to alternative antihypertensive therapy, taking into account security profile. Renal perfusion in the fetus, depending on the RAAS, develops from the second trimester of pregnancy, so the risk to the fetus increases when taking losartan in the II and III trimesters of pregnancy. Lactation period It is not known whether the excretion of amlodipine and / or losartan occurs in breast milk. In preclinical studies in animals, significant concentrations of amlodipine and / or the active metabolite of losartan in breast milk were noted. The use of the drug Lortenza® is contraindicated during breastfeeding. Fertility Amlodipine Reversible biochemical changes in the sperm head have been reported in some patients with calcium channel blockers. Clinical data on the potential effect of amlodipine on fertility is not enough. It was reported that in a study on rats, an adverse effect on the fertility of male rats was revealed. Losartan No mutagenic properties of losartan have been found in in vitro and in vivo studies. Fertility and reproductive function of male rats given oral doses up to 150 mg/kg/day did not change. When female rats were given doses of 100 mg/kg/day or more, a decrease in the number of corpus luteum, implants, and embryos was observed. Precautions Interaction with other drugs The antihypertensive effect of the drug Lortenza® may be enhanced when used simultaneously with other antihypertensive drugs. Therefore, the simultaneous use of various antihypertensive drugs should be justified. Amlodipine The simultaneous use of amlodipine with thiazide diuretics, alpha-blockers or ACE inhibitors is considered safe. Unlike other BMCCs, no clinically significant interaction of amlodipine (III generation BMCC) was found when used simultaneously with NSAIDs, incl. and with indomethacin. It is possible to enhance the antihypertensive effect of BMCC with simultaneous use with thiazide and “loop” diuretics, ACE inhibitors and nitrates, as well as with simultaneous use with alpha1-blockers, antipsychotics. The simultaneous use of amlodipine with inhibitors of the CYP3A4 isoenzyme requires careful monitoring of symptoms of arterial hypotension and peripheral edema. With the simultaneous use of diltiazem at a dose of 180 mg / day and amlodipine at a dose of 5 mg / day in elderly patients, the systemic exposure of amlodipine increases by 60%. Erythromycin, with simultaneous use, increases the Cmax of amlodipine in plasma in young patients by 22%, and in elderly patients by 50%. At the same time, strong inhibitors of the CYP3A4 isoenzyme (ketoconazole, itraconazole, ritonavir) can increase the concentration of amlodipine in blood plasma to an even greater extent. Despite the fact that an accurate quantitative assessment of the interaction of amlodipine and inducers of the CYP3A4 isoenzyme (for example, rifampicin, St. John’s wort) has not been obtained, against the background of their simultaneous use, regular monitoring of blood pressure is recommended. Beta-blockers, when used simultaneously with amlodipine, can exacerbate the course of CHF. Although a negative inotropic effect has not generally been observed with amlodipine, some BMCs may increase the negative inotropic effect of antiarrhythmic agents that cause QT prolongation (eg, amiodarone and quinidine). A single dose of sildenafil at a dose of 100 mg in patients with arterial hypertension does not affect the pharmacokinetic parameters of amlodipine. Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin. Ethanol (drinks containing alcohol): amlodipine, with a single and repeated use at a dose of 10 mg, does not affect the pharmacokinetics of ethanol. Antipsychotics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives. With the on / in the introduction of dantrolene during therapy with amlodipine, collapse, arrhythmias, a decrease in the strength of heart contractions and hyperkalemia are possible. Calcium preparations can reduce the antihypertensive effect of BMCC. With the simultaneous use of amlodipine with lithium preparations, it is possible to increase the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). Amlodipine does not change the pharmacokinetics of cyclosporine. It does not affect the serum concentration of digoxin and its renal clearance. It does not significantly affect the action of warfarin (prothrombin time). Cimetidine does not affect the pharmacokinetics of amlodipine. In in vitro studies, amlodipine does not affect plasma protein binding of digoxin, phenytoin, warfarin and indomethacin. Simultaneous single intake of 240 ml of grapefruit juice and amlodipine inside at a dose of 10 mg is not accompanied by a significant change in the pharmacokinetics of amlodipine. A single dose of aluminum- or magnesium-containing antacids does not significantly affect the pharmacokinetics of amlodipine. Losartan As with other drugs that block the formation of angiotensin II and its effects, the simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone), potassium preparations and potassium-containing salt substitutes can lead to an increase in serum potassium. As with the use of other drugs that affect the excretion of sodium, losartan can reduce the excretion of lithium, therefore, with the simultaneous use of lithium preparations and angiotensin II receptor antagonists, it is necessary to carefully monitor the concentration of lithium in the blood serum. In some patients with impaired renal function who received treatment with NSAIDs, including selective COX-2 inhibitors, the simultaneous use of ACE inhibitors and / or angiotensin II receptor antagonists, including losartan, may cause a further deterioration in renal function up to the development of acute renal failure. Usually this effect is reversible. NSAIDs, including selective COX-2 inhibitors, may reduce the effect of angiotensin II receptor antagonists, including losartan. Therefore, the antihypertensive effect of angiotensin II receptor antagonists may be weakened by the simultaneous use of NSAIDs, in particular, selective COX-2 inhibitors. Thus, the simultaneous use of the combination of amlodipine / losartan with NSAIDs should be carried out with caution in patients with impaired renal function. Dual RAAS blockade (simultaneous use of ACE inhibitors and angiotensin II receptor antagonists) in patients with atherosclerosis, CHF, or diabetes mellitus with target organ damage is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared with the use of the drug of one of the listed groups. Double blockade of the RAAS is possible only in selected cases under careful monitoring of renal function. The simultaneous use of losartan with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (CC less than 60 ml / min) and is not recommended in other patients. There was no pharmacokinetically significant interaction of losartan with drugs such as hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Taking rifampicin, an inducer of drug metabolism, reduces plasma concentrations of losartan and its active metabolite. In clinical studies, the use of two inhibitors of the CYP3A4 isoenzyme has been studied. Ketoconazole did not affect the metabolism of losartan to the active metabolite following intravenous administration of losartan. Erythromycin had no clinically significant effect on the pharmacokinetics of losartan when administered orally. Fluconazole, an inhibitor of CYP2C9, reduces the concentration of the active metabolite of losartan and increases the concentration of losartan in blood plasma, however, the pharmacodynamic significance of the simultaneous use of losartan and CYP2C9 inhibitors has not been established. It has been shown that in patients whose body does not convert losartan to an active metabolite, there is a very rare and specific defect in the CYP2C9 isoenzyme. These data suggest that the metabolism of losartan to the active metabolite is mediated predominantly by the CYP2C9 isoenzyme, and not by the CYP3A4 isoenzyme. Contraindications Severe liver failure (more than 9 points on the Child-Pugh scale); Hemodynamically pronounced stenosis of the aortic orifice; Hemodynamically unstable heart failure after acute myocardial infarction; Shock (including cardiogenic shock); Severe arterial hypotension (systolic blood pressure less than 90 mm Hg); Severe renal dysfunction (CC less than 20 ml / min), use in patients on hemodialysis; Simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (CC less than 60 ml / min); Pregnancy; The period of breastfeeding; Age up to 18 years (efficacy and safety not established); Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome; Hypersensitivity to the active ingredients and / or auxiliary components of the drug. CompositionAmlodipine besylate (amlodipine besylate) 6.94 mg, equivalent to amlodipine – 5 mg, losartan A substance (granules) 327.1 mg, contains losartan potassium – 100 mg. Excipients: cellactose 80 (lactose monohydrate – 75%, cellulose – 25%) – 72.9 mg; MCC – 212.96 mg mg; pregelatinized starch – 54 mg; sodium carboxymethyl starch – 22 mg; iron dye yellow oxide (E172) – 0.4 mg; colloidal silicon dioxide – 2.1 mg; magnesium stearate – 6.6 mg. Overdose Cases of overdose with the fixed combination of amlodipine / losartan are unknown. The following are data on overdose of amlodipine and losartan taken separately. Amlodipine Symptoms: a pronounced decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of developing severe and persistent arterial hypotension, including with the development of shock and death). Treatment: administration of activated charcoal (the use of activated charcoal in healthy volunteers immediately or within 2 hours after ingestion of 10 mg of amlodipine led to a significant decrease in its absorption). If necessary, gastric lavage is indicated. Clinically significant arterial hypotension with an overdose of amlodipine requires a set of measures to normalize the state of the cardiovascular system, it is necessary to give an elevated position to the lower extremities, to constantly monitor the functional parameters of the heart and respiratory system, BCC and diuresis. Conduct intensive symptomatic therapy. To restore vascular tone and blood pressure, vasoconstrictor drugs are used (in the absence of contraindications to their use), in order to eliminate the blockade of calcium channels – intravenous administration of calcium gluconate. Hemodialysis is ineffective. Losartan There are limited data on overdose of losartan. Symptoms: pronounced decrease in blood pressure, tachycardia, bradycardia due to parasympathetic (vagal) stimulation. Treatment: with the development of symptomatic arterial hypotension, supportive therapy is carried out. Hemodialysis for losartan and its active metabolite is ineffective. Side effectsWHO classification of the incidence of side effects: very often (?1/10), often (from?1/100 to <1/10), infrequently (from?1/1000 to <1/100), rarely (from?1 /10,000 to <1/1000), very rare (<1/10,000), frequency unknown (cannot be estimated from available data). Undesirable effects Frequency of development Amlodipine Losartan Infectious and parasitic diseases Urinary tract infection - Frequency unknown On the part of the hematopoietic system Leukopenia Very rare - Thromboc